Astrocytes are the most abundant cells in the central nervous system (CNS). Under normal conditions astrocytes modulate synaptic activity, and provide nutrients and support needed for neuronal survival1-4. In the context of neuroinflammation, astrocytes control CNS infiltration by peripheral pro-inflammatory leukocytes5-8 and regulate the activity of microglia, oligodendrocytes and cells of the adaptive immune system9. Thus, it is important to characterize the mechanisms regulating astrocyte activation during CNS inflammation, as well as potential targets for the therapeutic modulation of astrocyte activity.
Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease of the CNS. In most patients, MS initially presents a relapsing-remitting clinical course (relapsing-remitting MS, RRMS) that is followed by a progressive phase (secondary progressive MS, SPMS) characterized by a continued and irreversible accumulation of disability in which available treatments show limited efficacy10. Recent findings suggest that the local CNS innate immune response drives disease progression in SPMS9,11,12.